Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal piglets

Background: Supplementation of total parenteral nutrition (TPN) with a mixture of short-chain fatty acids (SCFA) enhances intestinal adaptation in the adult rodent model. However, the ability and timing of SCFA to augment adaptation in the neonatal intestine is unknown. Furthermore, the specific SCFA inducing the intestinotrophic effects and underlying regulatory mechanism(s) are unclear. Therefore, we examined the effect of SCFA supplemented TPN on structural aspects of intestinal adaptation and hypothesized that butyrate is the SCFA responsible for these effects. Methods: Piglets (n = 120) were randomized to (1) control TPN or TPN supplemented with (2) 60 mmol/L SCFA (36 mmol/L acetate, 15 mmol/L propionate and 9 mmol/L butyrate), (3) 9 mmol/L butyrate, or (4) 60 mmol/L butyrate. Within each group, piglets were further randomized to examine acute (4, 12, or 24 hours) and chronic (3 or 7 days) adaptations. Indices of intestinal adaptation, including crypt-villus architecture, proliferation and apoptosis, and concentration of the intestinotrophic peptide, glucagon-like pepide-2 (GLP-2), were measured. Results: Villus height was increased (P < .029) within 4 hours by supplemented TPN treatments. Supplemented TPN treatments increased (p < .037) proliferating cell nuclear antigen expression along the entire intestine. Indicative of an antiapoptotic profile, jejunal Bax:Bcl-w abundance was decreased (p = .033) by both butyrate-supplemented TPN treatments, and ileal abundance was decreased (p = .0002) by all supplemented TPN treatments, regardless of time. Supplemented TPN treatments increased (p = .016) plasma GLP-2 concentration at all time points. Conclusions: Butyrate is the SCFA responsible for augmenting structural aspects of intestinal adaptations by increasing proliferation and decreasing apoptosis within 4 hours postresection. The. intestinotrophic mechanism(s) underlying butyrate's effects may involve GLP-2. Ultimately, butyrate administration may enable an infant with short-bowel syndrome to successfully transition to enteral feedings by maximizing their absorptive area.